1 Ocak 2015 Dergi makalesi Açık Erişim

Erin, Nuray; Nizam, Esra; Tanriover, Gamze; Koksoy, Sadi

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/76477</identifier>
  <creators>
    <creator>
      <creatorName>Erin, Nuray</creatorName>
      <givenName>Nuray</givenName>
      <familyName>Erin</familyName>
      <affiliation>Akdeniz Univ, Sch Med, Dept Med Pharmacol, TR-07070 Antalya, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Nizam, Esra</creatorName>
      <givenName>Esra</givenName>
      <familyName>Nizam</familyName>
      <affiliation>Akdeniz Univ, Sch Med, Dept Med Pharmacol, TR-07070 Antalya, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Tanriover, Gamze</creatorName>
      <givenName>Gamze</givenName>
      <familyName>Tanriover</familyName>
      <affiliation>Akdeniz Univ, Sch Med, Dept Histol &amp; Embryol, TR-07070 Antalya, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Koksoy, Sadi</creatorName>
      <givenName>Sadi</givenName>
      <familyName>Koksoy</familyName>
      <affiliation>Akdeniz Univ, Sch Med, Dept Med Microbiol, TR-07070 Antalya, Turkey</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Autocrine Control Of Mip-2 Secretion From Metastatic Breast Cancer Cells Is Mediated By Cxcr2: A Mechanism For Possible Resistance To Cxcr2 Antagonists</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2015</publicationYear>
  <dates>
    <date dateType="Issued">2015-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/76477</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1007/s10549-015-3297-3</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">CXCR2 interacts with a wide range of chemokines and CXCR2 antagonists may have therapeutic value for treatment-resistant metastatic carcinomas. We aimed to explore regulation of activity of CXCR2 and its ligand, MIP-2, in metastatic breast carcinoma. We used mouse breast carcinoma cells metastasize to brain (4TBM), liver (4TLM), and heart (4THM) and explored the extra- and intracellular mechanisms effecting MIP-2 secretion using CXCR2 antagonist and inhibitors of downstream signaling molecules. 4TBM, 4TLM, and 4THM cells include cancer stem cell features and metastasize extensively. We also determined kinetics of MIP-2 secretion in 4T1 and non-metastatic 67NR mouse breast carcinoma cells. We found that there is an autocrine-inhibition of MIP-2 secretion. Specifically, metastatic cells selectively express CXCR2 only, and not CXCR1 and attenuating CXCR2 activity with SB225002 increased MIP-2 secretion. This may be due to the inhibition of protein kinase C (PKC) activity since RO318220; a specific inhibitor of PKC also increased MIP-2 secretion. Attenuating CXCR2 activity with SB225002, otherwise suppressed proliferation of 4THM and 4TBM cells. Tumor explants and cancer-associated fibroblasts obtained from 4TLM, 4THM, and 4TBM primary tumors secreted high levels of MIP-2. Surprisingly, CXCR2 expression was low in 4TLM cells demonstrating that liver metastatic cells might be resistant to the anti-tumoral effects of CXCR2 antagonists. Our results demonstrated that resistance to anti-proliferative effects of CXCR2 may also arise from feedback increases in MIP-2 secretion. Activation of PI3 K pathway augments MIP-2 secretion, hence possible resistance to the antitumor effects of CXCR2 antagonists might be prevented with inhibitors of PI3 K.</description>
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